Melanoma is the stuff of cancer nightmares. While treatable when locked in the skin’s outer layer, once it penetrates deeper and metastasizes in vital organs it turns deadly.

Israeli researchers have now discovered that fat cells play a key role in this transformation and have come up with a way to block it.

“We have answered a major question that has preoccupied scientists for years: What makes melanoma change form, turning aggressive and violent?” said Prof. Carmit Levy from Tel Aviv University, who led the study together with her colleague Tamar Golan.

“Melanoma turns fatal when it ‘wakes up,’ sending cancer cells to the dermis layer of skin, below the epidermis, and metastasizing in vital organs. Blocking the transformation of melanoma is one of the primary targets of cancer research today, and we now know fat cells are involved in this change.”

In their study, published in Science Signaling, the researchers examined dozens of biopsy samples taken from melanoma patients at Wolfson Medical Center and Tel Aviv Medical Center and observed fat cells near the tumor sites.

“We asked ourselves what fat cells were doing there and began to investigate,” says Levy. “We placed the fat cells on a petri dish near melanoma cells and followed the interactions between them.”

The researchers observed fat cells transferring proteins called cytokines, which affect gene expression, to the melanoma cells.

Prof. Carmit Levy, left, and Dr. Tamar Golan of Tel Aviv University. Photo: courtesy

Their experiments showed that the cytokines reduce the expression of a gene that in turn inhibits the expression of a key melanoma receptor, allowing the tumor to absorb a high concentration of the TGF beta protein, which stimulates melanoma cells and makes them aggressive.

But the process was found to be reversible. “When we removed the fat cells from the melanoma, the cancer cells calmed down and stopped migrating,” Levy explained.

After the petri-dish trial, a trial of mouse models of melanoma yielded similar results.

In the search for a potential drug based on the new discovery, the researchers experimented with therapies that are known to inhibit cytokines and TGF beta, but which have never been used to treat melanoma.

“We are talking about substances that are currently being studied as possible treatments for pancreatic cancer, and are also in clinical trials for prostate, breast, ovarian, and bladder cancers,” Golan said. “We saw that they restrained the metastatic process, and that the melanoma returned to its relatively ‘calm’ and dormant state.”

Levy believes the findings can serve as a basis for the development of new drugs to halt the spread of melanoma – therapies that already exist, but were never used for this purpose.

“In the future, we are seeking to collaborate with drug companies to enhance the development of the metastatic melanoma prevention approach.”